Cyclophosphamide (CP), an oxazaphosphorine-type of cytotoxic pro-drug (including ifosfamide, mafosfamide, and trofosfamide), is the single most commonly utilized component in (i) conventional chemotherapy and (ii) high-dose chemotherapy/bone marrow transplant/stem-cell rescue regiments for cancer treatments [1-5]. The activation through the hydroxylation of CP by microsomal cytochrome P450 enzymes in liver, leads to 4-hydroxycyclophosphamide (4-OHCP) (FIG. 1), and ultimately to the formation of cytotoxic phosphoramide mustard which alkylates DNA, thus preventing the proliferation of tumor cells [1-5]. There are, however, side reactions on this pathway leading to the enzyme inactivation and toxic byproducts causing systemic toxicity. Thus, in order to increase the efficacy of the pro-drug at less toxic doses, it would be beneficial to localize the production of cytotoxic metabolites at the tumor site.